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Neurologic Clinics Feb 2023Dysautonomias are a heterogenous group of disorders that can cause variable symptoms ranging from isolated impairment of one autonomic function to multisystem failure.... (Review)
Review
Dysautonomias are a heterogenous group of disorders that can cause variable symptoms ranging from isolated impairment of one autonomic function to multisystem failure. The causes are also diverse and can be central or peripheral and primary (owing to an intrinsic neurologic cause) or secondary (owing to a disorder that secondarily causes damage to the autonomic nervous system). This review covers common phenotypes of dysautonomias, primary and secondary causes, initial clinical workups, interpretation of common autonomic tests, and first-line treatments. A brief review of autonomic impairment associated with acute and long-COVID is also presented.
Topics: Humans; COVID-19; Primary Dysautonomias; Post-Acute COVID-19 Syndrome
PubMed: 36400555
DOI: 10.1016/j.ncl.2022.08.002 -
Muscle & Nerve Jan 2021Autonomic neuropathies represent a complex group of disorders that preferentially target autonomic fibers and can be classified as either acute/subacute or chronic in... (Review)
Review
Autonomic neuropathies represent a complex group of disorders that preferentially target autonomic fibers and can be classified as either acute/subacute or chronic in onset. Acute-onset autonomic neuropathies manifest with such conditions as paraneoplastic syndromes, Guillain-Barre syndrome, Sjögren syndrome, infection, or toxins/chemotherapy. When the presentation is acute, immune-mediated, and without a secondary cause, autoimmune autonomic ganglionopathy is likely, and should be considered for immunotherapy. Of the chronic-onset forms, diabetes is the most widespread and disabling, with autonomic impairment portending increased mortality and cardiac wall remodeling risk. Acquired light chain (AL) and transthyretin (TTR) amyloidosis represent two other key etiologies, with TTR amyloidosis now amenable to newly-approved gene-modifying therapies. The COMPASS-31 questionnaire is a validated outcome measure that can be used to monitor autonomic severity and track treatment response. Symptomatic treatments targeting orthostatic hypotension, among other symptoms, should be individualized and complement disease-modifying therapy, when possible.
Topics: Amyloid Neuropathies, Familial; Autoimmune Diseases of the Nervous System; Autonomic Nervous System; Autonomic Nervous System Diseases; Humans; Peripheral Nervous System Diseases; Prealbumin
PubMed: 32926436
DOI: 10.1002/mus.27048 -
Seminars in Neurology Oct 2020Paroxysmal sympathetic hyperactivity (PSH) is a relatively common, but often unrecognized, complication of acute diffuse or multifocal brain diseases, most frequently... (Review)
Review
Paroxysmal sympathetic hyperactivity (PSH) is a relatively common, but often unrecognized, complication of acute diffuse or multifocal brain diseases, most frequently encountered in young comatose patients with severe traumatic brain injury. It is presumed to be caused by loss of cortical inhibitory modulation of diencephalic and brain stem centers and possible additional maladaptive changes in the spinal cord that combine to produce exaggerated sympathetic responses to stimulation. The syndrome consists of repeated sudden episodes of tachycardia, tachypnea, hypertension, sweating, and sometimes fever and dystonic posturing. The diagnosis is clinical. Treatment includes reducing any external stimulation that can trigger the episodes, and starting abortive (e.g., intravenous morphine) and preventive medications (e.g., gabapentin, propranolol, clonidine). Prompt and adequate treatment of PSH may reduce the likelihood of secondary complications, such as dehydration, weight loss and malnutrition, and muscle contractures.
Topics: Autonomic Nervous System Diseases; Humans; Sympathetic Nervous System
PubMed: 32906174
DOI: 10.1055/s-0040-1713845 -
Continuum (Minneapolis, Minn.) Feb 2020This article provides a summary of the autonomic neuropathies, including neuropathies associated with diabetes mellitus, neuropathies due to amyloid deposition,... (Review)
Review
PURPOSE OF REVIEW
This article provides a summary of the autonomic neuropathies, including neuropathies associated with diabetes mellitus, neuropathies due to amyloid deposition, immune-mediated autonomic neuropathies (including those associated with a paraneoplastic syndrome), inherited autonomic neuropathies, and toxic autonomic neuropathies. The presenting features, diagnostic investigations, and natural history of these neuropathies are discussed.
RECENT FINDINGS
Recent findings in autonomic peripheral neuropathy include data on the epidemiology and atypical presentations of diabetic autonomic neuropathy, treatment-induced neuropathy of diabetes mellitus, the presentation of immune-mediated neuropathies, and advances in hereditary neuropathy associated with amyloidosis and other hereditary neuropathies.
SUMMARY
Knowledge and recognition of the clinical features of the autonomic neuropathies, combined with appropriate laboratory and electrophysiologic testing, will facilitate accurate diagnosis and management.
Topics: Autonomic Nervous System; Autonomic Nervous System Diseases; Diabetic Neuropathies; Disease Progression; Genetic Diseases, Inborn; Humans; Peripheral Nervous System Diseases
PubMed: 31996622
DOI: 10.1212/CON.0000000000000825 -
Neurobiology of Disease Feb 2020Parkinson's disease (PD) is a neurodegenerative disease with a 200 year-long research history. Our understanding about its clinical phenotype and pathogenesis remains... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disease with a 200 year-long research history. Our understanding about its clinical phenotype and pathogenesis remains limited, although dopaminergic replacement therapy has significantly improved patient outcomes. Autonomic dysfunction is an essential category of non-motor phenotypes that has recently become a cutting edge field that directs frontier research in PD. In this review, we initially describe the epidemiology of dysautonomic symptoms in PD. Then, we perform a meticulous analysis of the pathophysiology of autonomic dysfunction in PD and propose that the peripheral autonomic nervous system may be a key route for α-synuclein pathology propagation from the periphery to the central nervous system. In addition, we recommend that constipation, orthostatic hypotension, urinary dysfunction, erectile dysfunction, and pure autonomic failure should be viewed as prodromal dysautonomic markers in PD prediction and diagnosis. Finally, we summarize the strategies currently available for the treatment of autonomic dysfunction in PD and suggest that high-quality, better-designed, randomized clinical trials should be conducted in the future.
Topics: Animals; Autonomic Nervous System; Autonomic Nervous System Diseases; Humans; Mice; Parkinson Disease
PubMed: 31809788
DOI: 10.1016/j.nbd.2019.104700 -
Continuum (Minneapolis, Minn.) Feb 2020This article reviews the anatomic, functional, and neurochemical organization of the sympathetic and parasympathetic outputs; the effects on target organs; the central... (Review)
Review
PURPOSE OF THE REVIEW
This article reviews the anatomic, functional, and neurochemical organization of the sympathetic and parasympathetic outputs; the effects on target organs; the central mechanisms controlling autonomic function; and the pathophysiologic basis for core symptoms of autonomic failure.
RECENT FINDINGS
Functional neuroimaging studies have elucidated the areas involved in central control of autonomic function in humans. Optogenetic and other novel approaches in animal experiments have provided new insights into the role of these areas in autonomic control across behavioral states, including stress and the sleep-wake cycle.
SUMMARY
Control of the function of the sympathetic, parasympathetic, and enteric nervous system functions depends on complex interactions at all levels of the neuraxis. Peripheral sympathetic outputs are critical for maintenance of blood pressure, thermoregulation, and response to stress. Parasympathetic reflexes control lacrimation, salivation, pupil response to light, beat-to-beat control of the heart rate, gastrointestinal motility, micturition, and erectile function. The insular cortex, anterior and midcingulate cortex, and amygdala generate autonomic responses to behaviorally relevant stimuli. Several nuclei of the hypothalamus generate coordinated patterns of autonomic responses to internal or social stressors. Several brainstem nuclei participate in integrated control of autonomic function in relationship to respiration and the sleep-wake cycle. Disorders affecting the central or peripheral autonomic pathways, or both, manifest with autonomic failure (including orthostatic hypotension, anhidrosis, gastrointestinal dysmotility, and neurogenic bladder or erectile dysfunction) or autonomic hyperactivity, primary hypertension, tachycardia, and hyperhidrosis.
Topics: Animals; Autonomic Nervous System; Autonomic Nervous System Diseases; Brain; Humans
PubMed: 31996619
DOI: 10.1212/CON.0000000000000817 -
Neurotherapeutics : the Journal of the... Oct 2020Recognition of the importance of nonmotor dysfunction as a component of Parkinson's disease has exploded over the past three decades. Autonomic dysfunction is a frequent... (Review)
Review
Recognition of the importance of nonmotor dysfunction as a component of Parkinson's disease has exploded over the past three decades. Autonomic dysfunction is a frequent and particularly important nonmotor feature because of the broad clinical spectrum it covers. Cardiovascular, gastrointestinal, urinary, sexual, and thermoregulatory abnormalities all can appear in the setting of Parkinson's disease. Cardiovascular dysfunction is characterized most prominently by orthostatic hypotension. Gastrointestinal dysfunction can involve virtually all levels of the gastrointestinal tract. Urinary dysfunction can entail either too frequent voiding or difficulty voiding. Sexual dysfunction is frequent and frustrating for both patient and partner. Alterations in sweating and body temperature are not widely recognized but often are present. Autonomic dysfunction can significantly and deleteriously impact quality of life for individuals with Parkinson's disease. Because effective treatment for many aspects of autonomic dysfunction is available, it is vitally important that assessment of autonomic dysfunction be a regular component of the neurologic history and exam and that appropriate treatment be initiated and maintained.
Topics: Autonomic Nervous System Diseases; Cardiovascular Diseases; Gastrointestinal Diseases; Humans; Hypotension, Orthostatic; Parkinson Disease; Sexual Dysfunction, Physiological
PubMed: 32789741
DOI: 10.1007/s13311-020-00897-4 -
Ageing Research Reviews Feb 2023Parkinson's Disease (PD) is a neurodegenerative disorder that affects dopaminergic neurons in the mesencephalic substantia nigra, causing a progressive clinical course... (Review)
Review
Parkinson's Disease (PD) is a neurodegenerative disorder that affects dopaminergic neurons in the mesencephalic substantia nigra, causing a progressive clinical course characterized by pre-motor, non-motor and motor symptoms, which negatively impact the quality of life of patients and cause high health care costs. Therefore, the present study aims to discuss the clinical manifestations of PD and to make a correlation with the gut-brain (GB) axis, approaching epidemiology and therapeutic perspectives, to better understand its clinical progression and identify symptoms early. A literature review was performed regarding the association between clinical progression, the gut-brain axis, epidemiology, and therapeutic perspectives, in addition to detailing pre-motor, non-motor symptoms (neuropsychiatric, cognitive, autonomic, sleep disorders, sensory abnormalities) and cardinal motor symptoms. Therefore, this article addresses a topic of extreme relevance, since the previously mentioned clinical manifestations (pre-motor and non-motor) can often act as prodromal markers for the early diagnosis of PD and may precede it by up to 20 years.
Topics: Humans; Parkinson Disease; Quality of Life; Cognition Disorders; Cognitive Dysfunction; Autonomic Nervous System Diseases; Disease Progression
PubMed: 36581178
DOI: 10.1016/j.arr.2022.101834 -
Clinical Neurology and Neurosurgery Jan 2022Traumatic brain injury (TBI) is one of the leading causes of disability, morbidity, and mortality worldwide. Some of the more common etiologies of TBI include closed... (Review)
Review
Traumatic brain injury (TBI) is one of the leading causes of disability, morbidity, and mortality worldwide. Some of the more common etiologies of TBI include closed head injury, penetrating head injury, or an explosive blast head injury. Neuronal damage in TBI is related to both primary injury (caused by mechanical forces), and secondary injury (caused by the subsequent tissue and cellular damages). Recently, it has been well established that Paroxysmal Sympathetic Hyperactivity (PSH), also known as "Sympathetic Storm", is one of the main causes of secondary neuronal injury in TBI patients. The clinical manifestations of PSH include recurrent episodes of sympathetic hyperactivity characterized by tachycardia, systolic hypertension, hyperthermia, tachypnea with hyperpnea, and frank diaphoresis. Given the diverse manifestations of PSH and its notable impact on the outcome of TBI patients, we have comprehensively reviewed the current evidence and discussed the pathophysiology, clinical manifestations, time of onset and duration of PSH during TBI. This article reviews the different types of head injuries that most commonly lead to PSH, possible approaches to manage and minimize PSH complications in TBI and the current prognosis and outcomes of PSH in TBI patients.
Topics: Autonomic Nervous System Diseases; Brain Injuries, Traumatic; Humans; Sympathetic Nervous System
PubMed: 34861468
DOI: 10.1016/j.clineuro.2021.107081 -
Arquivos Brasileiros de Cardiologia Apr 2021Dysautonomia covers a range of clinical conditions with different characteristics and prognoses. They are classified as Reflex Syndromes, Postural Orthostatic...
Dysautonomia covers a range of clinical conditions with different characteristics and prognoses. They are classified as Reflex Syndromes, Postural Orthostatic Tachycardia Syndrome (POTS), Chronic Fatigue Syndrome, Neurogenic Orthostatic Hypotension (nOH) and Carotid Sinus Hypersensitivity Syndrome. Reflex (vasovagal) syndromes will not be discussed in this article. Reflex (vasovagal) syndromes are mostly benign and usually occur in patients without an intrinsic autonomic nervous system (ANS) or heart disease. Therefore, they are usually studied separately. Cardiovascular Autonomic Neuropathy (CAN) is the term most currently used to define dysautonomia with impairment of the sympathetic and/or parasympathetic cardiovascular autonomic nervous system. It can be idiopathic, such as multisystemic atrophy or pure autonomic failure, or secondary to systemic pathologies such as diabetes mellitus, neurodegenerative diseases, Parkinson's disease, dementia syndromes, chronic renal failure, amyloidosis and it may also occur in the elderly. The presence of Cardiovascular Autonomic Neuropathy (CAN) implies greater severity and worse prognosis in various clinical situations. Detection of Orthostatic Hypotension (OH) is a late sign and means greater severity in the context of dysautonomia, defined as Neurogenic Orthostatic Hypotension (nOH). It must be differentiated from hypotension due to hypovolemia or medications, called non-neurogenic orthostatic hypotension (nnOH). OH can result from benign causes, such as acute, chronic hypovolemia or use of various drugs. However, these drugs may only reveal subclinical pictures of Dysautonomia. All drugs of patients with dysautonomic conditions should be reevaluated. Precise diagnosis of CAN and the investigation of the involvement of other organs or systems is extremely important in the clinical suspicion of pandysautonomia. In diabetics, in addition to age and time of disease, other factors are associated with a higher incidence of CAN, such poor glycemic control, hypertension, dyslipidemia and obesity. Among diabetic patients, 38-44% can develop Dysautonomia, with prognostic implications and higher cardiovascular mortality. In the initial stages of DM, autonomic dysfunction involves the parasympathetic system, then the sympathetic system and, later on, it presents as orthostatic hypotension. Valsalva, Respiratory and Orthostatic tests (30:15) are the gold standard methods for the diagnosis of CAN. They can be associated with RR Variability tests in the time domain, and mainly in the frequency domain, to increase the sensitivity (protocol of the 7 tests). These tests can detect initial or subclinical abnormalities and assess severity and prognosis. The Tilt Test should not be the test of choice for investigating CAN at an early stage, as it detects cases at more advanced stages. Tilt response with a dysautonomic pattern (gradual drop in blood pressure without increasing heart rate) may suggest CAN. Treatment of patients at moderate to advanced stages of dysautonomia is quite complex and often refractory, requiring specialized and multidisciplinary evaluation. There is no cure for most types of Dysautonomia at a late stage. NOH patients can progress with supine hypertension in more than 50% of the cases, representing a major therapeutic challenge. The immediate risk and consequences of OH should take precedence over the later risks of supine hypertension and values greater than 160/90 mmHg are tolerable. Sleeping with the head elevated (20-30 cm), not getting up at night, taking short-acting antihypertensive drugs for more severe cases, such as losartan, captopril, clonidine or nitrate patches, may be necessary and effective in some cases. Preventive measures such as postural care; good hydration; higher salt intake; use of compression stockings and abdominal straps; portioned meals; supervised physical activity, mainly sitting, lying down or exercising in the water are important treatment steps. Various drugs can be used for symptomatic nOH, especially fludrocortisone, midodrine and droxidopa, the latter not available in Brazil. The risk of exacerbation or triggering supine hypertension should be considered. Chronic Fatigue Syndrome represents a form of Dysautonomia and has been renamed as a systemic disease of exercise intolerance, with new diagnostic criteria: 1 - Unexplained fatigue, leading to occupational disability for more than 6 months; 2 - Feeling ill after exercising; 3 - Non-restorative sleep; 4 - One of the following findings: cognitive impairment or orthostatic intolerance. Several pathologies today have evolved with chronic fatigue, being called chronic diseases associated with chronic fatigue. Postural orthostatic tachycardia syndrome (POTS), another form of presentation of dysautonomic syndromes, is characterized by sustained elevation of heart rate (HR) ≥30 bpm (≥40 bpm if <20 years) or HR ≥120 bpm, in the first 10 minutes in an orthostatic position or during the tilt test, without classical orthostatic hypotension associated. A slight decrease in blood pressure may occur. Symptoms appear or get worse in an orthostatic position, with dizziness, weakness, pre-syncope, palpitations, and other systemic symptoms being common.
Topics: Aged; Autonomic Nervous System Diseases; Brazil; Droxidopa; Humans; Hypotension, Orthostatic; Tilt-Table Test
PubMed: 33886735
DOI: 10.36660/abc.20200420